Lyme disease ophthalmic manifestations are underestimated due to a wide variety of clinical presentations and a lack of robust evidence. We performed a systematic review and meta-analysis to analyze the prevalence of ocular findings in patients diagnosed with Lyme Disease. This systematic review and meta-analysis was conducted following PRISMA guidelines. We systematically searched PubMed, Embase, Lilacs, and the Cochrane Central Register of Controlled Trials databases for studies enrolling patients diagnosed with Lyme disease who exhibited ocular manifestations until April 2024. The latest version of the Newcastle-Ottawa Scale (NOS) was utilized to evaluate the risk of bias. All statistical analyses were performed using RStudio statistical software version 4.3.2. Heterogeneity was assessed using I² statistics. A total of 21 studies were included, comprising 859 patients. The population was mostly male (52%), with a mean follow-up of 4.6 ± 3.14 years. Diplopia and strabismus were assessed in only five studies, yet they were the most reported ocular manifestations, with a prevalence of 50.74% (CI: 36.73-65.61; I² = 10%). Anterior segment findings, including conjunctivitis, keratitis, and cataracts, had a pooled incidence of 23.76% (CI: 13.83-37.71; I² = 76%). Ten studies analyzed posterior segment findings, which included retinitis, chorioretinitis, neuroretinitis, posterior uveitis, intermediate uveitis, and retinal vasculitis, resulting in an overall prevalence of 19.66% (CI: 7.87-41.23; I² = 74%). Third cranial nerve palsy was found in 18.65% of the cases (CI: 8.91-34.95; I² = 62%), while optic nerve findings were present in 10.76% of the cases (CI: 5.43-20.22; I² = 24%). The results of this systematic review and meta-analysis including over 859 patients suggest that ocular findings in Lyme disease such as conjunctivitis, anterior uveitis, strabismus and diplopia) are common and should raise the suspicion of infection even before serological diagnosis.

Lyme disease, a multisystem infectious process instigated by the spirochete Borrelia burgdorferi sensu lato complex, remains a formidable clinical entity due to its protean systemic manifestations. Cardiac involvement, termed Lyme carditis, represents an uncommon yet potentially critical complication of disseminated early infection, characterized by spirochetal infiltration of cardiac tissues precipitating a spectrum of conduction abnormalities and myocardial inflammation. This article synthesizes contemporary understanding of the molecular pathogenesis underlying Borrelia-mediated cardiotropism, focusing on post-infectious inflammatory cascades and potential persistent immunogenic stimuli. Clinical presentation is critically examined, emphasizing the diagnostic challenges posed by variable symptomology ranging from subclinical conduction delays to high-grade atrioventricular block and, rarely, myopericarditis. The discourse advances to a nuanced analysis of current therapeutic strategies, juxtaposing guideline-recommended antibiotic regimens against complex presentations necessitating advanced cardiac interventions, such as temporary pacing. Furthermore, the manuscript engages with emergent debates concerning post-treatment Lyme disease syndrome (PTLDS) and its potential cardiological correlates, a domain requiring further delineation. By integrating recent epidemiological data and advanced diagnostic modalities, including serological interpretation and novel imaging techniques, this review aims to provide a comprehensive, evidence-based framework for the recognition and management of this intriguing cardioneuropathic syndrome, thereby mitigating the risk of long-term cardiac morbidity.

BackgroundCutaneous Lyme disease presents differently in light versus dark skin, and delayed diagnosis can increase outcome severity. Insufficient exposure to manifestations of Lyme disease in dark skin during medical training may contribute to health inequities due to late or missed diagnoses. It remains unclear how Lyme disease, specifically, is represented in commonly used medical training materials. To inform curricula updates, we identified primary educational resources used for teaching dermatology at top-tier U.S. medical schools and assessed the representation of erythema migrans on light and dark skin in these materials.MethodsIn this cross-sectional content analysis, commonly used training resources for 50 top U.S. medical schools were identified by reviewing websites and syllabi and contacting schools when information was unavailable. Resource images were categorized as “light-skinned” or “dark-skinned” using the Fitzpatrick scale (I-III vs IV-VI). Proportions and counts of light-skinned and dark-skinned images were compared to U.S. demographics, resource format (print-/web-based), and age of publication (pre-/post-2020).ResultsSixteen resources, containing 47 erythema migrans images, were identified. Two of 16 (12.5%) resources included dark-skinned images; both were web-based resources. None of the print resources or those published before 2020 included dark-skinned images. The proportions of light-skinned (n = 44, 93.6%) and dark-skinned (n = 3, 6.4%) images were significantly different from U.S. demographics (p = .03).ConclusionsAmong commonly used medical student resources, few contain images of erythema migrans on dark skin; these were only found in web-based resources published since 2020. This differential representation has the potential to contribute to inequitable diagnosis and treatment across racial groups.

Running into the Lyme-light: a retrospective cross-sectional study of tick bites and Lyme disease prevalence, incidence, and prevention in hill runners, Scotland, UK.

ABSTRACTRational adjuvant selection is a systematic approach based on adjuvant-mediated immunomodulation to identify safe vaccine regimens that enhance protective immunity. Transmitted through ticks and caused by the bacteriumBorrelia burgdorferi(Bb), Lyme disease (LD) is the most common vector-borne disease in the Northern hemisphere. There are no effective vaccines, making it suitable for testing the concept of rational adjuvant selection. Here, we formulated our previously developed and effective LD vaccine antigen, CspZ-YAC187S,with different adjuvants suitable for human use; we analyzed the immune response by transcriptomics and tested the vaccine efficacy afterBbinfection. We identified Alum-CpG and Alum-αGal to elicit the highest titers of CspZ-YAC187S-dependent protective antibodies and robust levels of protection but through distinct mechanisms of immunomodulation. We demonstrated that immunization with Alum-CpG formulated CspZ-YAC187Sprovided up to nine months of protective bactericidal antibody titers, as well as recall-memory response to prevent LD after natural infection. Immunity was linked to elevated levels of IgG1 memory cells in the vaccine-triggered immune responses. This work thus identified a durable, memory immunity-driven LD vaccine, ultimately paving the road to understanding the mechanisms of rationale adjuvant selection for vaccine development.

BackgroundLyme disease (LD) is the most common tick-borne illness in the United States (US). Incidence peaks in older adults, yet LD-associated healthcare costs are understudied in this population. This retrospective, observational study assessed LD-associated healthcare costs among US Medicare Fee-for-Service (FFS) beneficiaries aged ≥ 65 years.MethodsEligible LD cases were identified in Medicare FFS claims data (Medicare Parts A, B, and D) from Jan 2016–Jul 2023, had continuous eligibility for the assessment period, and had ≥ 1 outpatient or inpatient LD claim. Outpatient claims had an LD diagnosis code (A69.xx) with qualifying antibiotic treatment within 30 days. Inpatient claims had a primary LD diagnosis code or a secondary LD diagnosis code with a primary LD-linked condition. Cases were classified into subgroups (localized, disseminated, indeterminate) based on LD-associated diagnosis codes, outpatient and inpatient services, and antibiotics. Outcomes included LD-specific (medical) costs during individual LD episodes and all-cause (medical and pharmacy) costs at 6-month follow-up versus 6-month baseline. Comparisons used a paired t test for continuous measures, with significance noted at P< 0.001.ResultsAmong 121,941 identified LD cases, 53.0% were female, 93.4% were White, and the mean (standard deviation) age was 74.0 (6.0) years. Of these, 62.2% had localized LD, 21.3% had disseminated LD, and 16.6% had indeterminate LD. Mean LD-specific total (medical) costs were $1,513 overall and were highest for disseminated cases ($4,554) (Figure 1). Mean all-cause total costs at 6-month follow-up versus 6-month baseline were significantly higher for LD cases overall (Δ$4,378), localized LD cases (Δ$2,638), disseminated LD cases (Δ$9,888), and indeterminate LD cases (Δ$3,841) (Figure 2).ConclusionUS Medicare FFS beneficiaries with LD incurred substantial healthcare costs, especially those with disseminated disease. Strategies to prevent LD cases in older adults may decrease associated economic burden.DisclosuresHolly Yu, MSPH, Pfizer Inc.: Employee; may hold company shares and/or stocks. Peter Kardel, MA, ADVI Health LLC: Employee; may hold company shares and/or stocks. Heidi De Souza, MPH, ADVI Health LLC: Employee; may hold company shares and/or stocks. L. Hannah Gould, PhD, MS, MBA, Pfizer Inc.: Employee; may hold company shares and/or stocks.

In this paper, we develop a periodic degenerate reaction-diffusion model of Lyme disease with seasonal and spatially heterogeneous structure in both host and tick populations. Moreover, the tick population is divided into three stages: larva, nymph and adult, each exhibiting distinct feeding preferences for two vertebrate hosts. We introduce the basic reproduction ratio R 0 for this model and establish that the disease-free periodic solution is globally asymptotically stable if R 0 < 1 , while the system admits a globally asymptotically stable positive periodic solution if 1 $ ]]> R 0 > 1 . Numerically, we investigate the spread of Lyme disease in Bulgaria. Simulations support our analytical findings and highlight the important role that environmental heterogeneity plays in the transmission dynamics of Lyme disease.

Lyme disease as a rare trigger for autoimmune hemolytic anemia.

Borrelia burgdorferi, one of the most prevalent tick-borne pathogens, can cause a complex and multisystem illness called Lyme disease, where there has been an unmet need for novel therapeutic or preventive strategies. We previously identified an essential protein-protein interaction (PPI) event in B. burgdorferi involving two unique proteins, BB0323 and BB0238; herein, we show that this PPI is indispensable for long-term borrelial survival in mammals and explore its potential as a novel target for small molecule therapeutics. Using X-ray crystallography, we solved the structure of the BB0238-BB0323 complex and identified the hotspot residues that form the biomolecular PPI interface area of ~1000 square Ångstroms. We then performed quantitative high-throughput drug screens of 62,740 diverse small molecules utilizing an amplified luminescent proximity homogeneous assay linked immunosorbent assay (AlphaLISA). Following a comprehensive pipeline to confirm small molecule hits, we short-listed three distinct PPI inhibitors of BB0238-BB0323. One of these inhibitors, called lomibuvir (VX-222, VCH-222), displayed robust PPI inhibition inside B. burgdorferi cells and was shown to affect pathogen persistence in a tick-borne murine model of Lyme disease. Our study highlights targeted PPI disruption as a new therapeutic strategy against B. burgdorferi and may foster future antimicrobial discovery efforts to resolve clinical complications associated with Lyme disease.

BosR is a novel nucleic acid-binding protein in the ferric uptake regulator (FUR) family that regulates gene expression in the Lyme disease spirochete Borrelia (Borreliella) burgdorferi. This issue of Molecular Microbiology contains a comprehensive transcriptomic study that keenly defines the regulatory swath of BosR in the vertebrate host of B. burgdorferi. Despite homology to Fur-like and PurR-like orthologs, BosR has traditionally been linked to regulation of RpoS, the alternative sigma factor that controls the regulon required for establishing a vertebrate infection. However, BosR regulates other genes through an RpoS-independent mechanism, which is elegantly elaborated in Grassmann etal., along with clearly demonstrating that BosR does not participate in the defense against oxidative and nitrosative stress in the vertebrate. However, the recently recognized role of BosR as an RNA-binding protein with RNA chaperone activity that regulates gene expression in a post-transcriptional fashion is not wholly appreciated, which clouds the results on determining the DNA-binding site invivo. Regardless, this seminal study enshrines BosR as a major regulator of gene expression in B. burgdorferi and delineates a multitude of BosR-regulated cellular functions in the spirochete related to its ability to navigate between its tick vector and vertebrate host in nature as well as to persist in these two disparate environments.

The main agent of Lyme borreliosis (LB) in North America, the bacteria Borrelia burgdorferi, is spreading in Canada following the northward expansion of its primary tick vectors, Ixodes scapularis and Ixodes pacificus. Despite the importance of this pathogen for human health, the precise geographical origin and genome structure of Canadian B. burgdorferi strains remain to be determined, and no complete genome sequence from this region is available. The complex genome structure of Borrelia species makes their assembly challenging, but the latest long-read sequencing technologies and bioinformatics software now enable de novo assembly of Borrelia genomes with high efficacy. In this study, we sequenced and assembled the genomes of six Canadian B. burgdorferi strains to compare their content and structure to additional Borrelia genomes from the USA and Europe. We successfully reconstructed the genome, comprising chromosomes and plasmids of the six Canadian strains. These genomes showed an overall similar structure compared to other B. burgdorferi strains. Phylogenetic inferences highlighted topological differences in the placement of B. burgdorferi strains between the chromosome and the cp26 and lp54 plasmids. Synteny analyses revealed important replicon sequence conservation across strains while highlighting a high proportion of shared gene sequences among the replicons of the same strain, especially for cp32 plasmids. We describe the first complete genomes of Canadian B. burgdorferi strains and present a strategy for the assembly, annotation, comparative analysis of plasmids and their evolution in the same bacterial genus. While the genome content and structure of Canadian strains are similar to other B. burgdorferi strains, the information in the plasmids and genes they harbour will be useful to elucidate the origins and evolution of LB in Canada.

Disentangling complex disease ecology networks: Using structural equation modelling to quantify the direct and indirect effects of deer on Lyme borreliosis hazard.

Lyme arthritis: Demographic characteristics and Borrelia ospA genospecies in synovial fluid. A 17-year cohort study in Sweden.

A total of 101 patients with a clinical picture of persisting Lyme disease seen at the University of Connecticut Health Center and Boston Medical Center were recruited for the study to determine whether persistent infection is the likely cause. Brain SPECT imaging and responses to antibiotic treatments were recorded. Patients had more than 5 symptoms lasting more than 6 months. A history of tick bite and/or rash was present in 40%. Western blots were more sensitive than enzyme immunoassays screening tests. Brain SPECT scans were abnormal in 65% of patients. Treatment with specific antibiotics over time resolved the illness in most children. A clinical diagnosis can be made based on the combination of certain persisting symptoms, and serologic and nuclear medicine studies support the clinical diagnosis. Treatment with specific antibiotics over a number of months is helpful as a diagnostic test and lead to resolution of symptoms in most patients.

Mapping ticks (Acari: Argasidae, Ixodidae) and informing local public action: Insights from the United Kingdom Tick Surveillance Scheme (2021-2024).

Lyme disease is caused by the host-adapted spirochete Borrelia burgdorferi. With a genome of only 1.5 mbp, B. burgdorferi is dependent on metabolites scavenged from their vertebrate and invertebrate hosts for growth. These scavenged nutrients include several lipid precursors: the spirochete is auxotrophic for fatty acids and cholesterol, and also accumulates environmental phospholipids. Comprehensive lipidomic analysis of B. burgdorferi by LC MS/MS was used to identify previously undescribed membrane components. These include some likely scavenged from the culture medium and some which may be synthesized de novo via unknown pathways. Changes in fatty acid composition as cells enter stationary phase suggest that scavenging of environmental lipids is preferential to de novo synthesis, while transcriptomics suggests that this may be due to the energetic cost of synthesizing glycerol phosphate precursors. In media supplemented with excess phospholipids, scavenged lipids can be found at high concentrations in cells, suggesting that the membranes of infecting bacteria are likely to be partly shaped by the host environment. Transcriptomic analysis also show a link between environmental lipids and the expression of virulence-associated surface lipoproteins including reciprocal regulation of ospA and ospC. Given that borrelial membrane lipids are known to be antigenic during infection, these findings identify potential new targets for the development of diagnostic tests or vaccines.

PurposeThe diagnosis of Lyme borreliosis (LB) can be challenging. The aim of this study was to investigate, describe and compare the actual use, application and documentation of LB serology in three neighbouring LB-endemic counties in Sweden. As part of this, we intended to study the concordance between laboratory reports and physicians’ assessments regarding LB.MethodsThree hundred patients sampled for LB serology in the counties of Jönköping, Kalmar and Östergötland, in 2016 were randomly selected for this study. Data was collected from the laboratory information technology systems of the departments of Clinical Microbiology in the three counties and from medical records.ResultsSuspected Lyme neuroborreliosis (LNB) was the most common indication for LB serology, and was found in a total of 188/300 (63%) patients: 75/100 in Jönköping, 66/100 in Östergötland and 47/100 in Kalmar. Cerebrospinal fluid examination was performed on a minority of patients in whom LNB was suspected, 34/188 (18%). LB serology was performed on sera from 15 patients with suspected erythema migrans. Sufficient information to enable an assessment of concordance between laboratory reports and medical records was available for 158/300 (53%) patients, while 94/158 (59%) were considered to have concordant records.ConclusionsLB serology is frequently performed on questionable indications contrary to guidelines, which limits the value and potential of the analysis. Notably, the use appears to be different in three neighbouring counties that follow the same national guidelines. Although new diagnostic technologies, may improve laboratory diagnostics in the future, there is still a need for interventions to enable a more rational use of LB serology.

Hard ticks are important vectors for several human and zoonotic pathogens, transmitting diseases such as Crimean–Congo hemorrhagic fever, Lyme disease, Kyasanur forest disease, Powassan virus disease, Tick-borne encephalitis, Rickettsiosis, and Anaplasmosis. Morphological identification of ticks relies on taxonomic keys but is often challenging due to damaged, engorged, or immature specimens and requires expertise. Molecular taxonomy can be a supplement to species identification and usually requires nucleotide sequencing of the genetic markers. PCR-RFLP is an important tool for tick identification and can be supplemented to the classical taxonomy. The current study focused on the morphological identification of important hard tick vectors from India, their phylogenetic positioning, and developing a PCR-RFLP based diagnostic tool for easy identification of hard tick vectors. The primer sets were designed to amplify the ITS-2 region from important tick vectors causing human and zoonotic diseases in India. These ticks were morphologically identified with taxonomical keys, and the extracted genomic DNA were used for ITS-2 based PCR amplification. The nucleotide sequences from each vector were used for their phylogenetic positioning. We obtained variable sizes of ITS-2 amplicons from each species and utilized the sequence for RFLP assays design. We have successfully shown PCR-RFLP based assays with two different restriction enzymes (Hae III & Rsa I) with specific restriction sites on the amplified regions. The PCR-RFLP tool showed different DNA fragment patterns on the agarose gel, specific for each hard tick vector. This study presents the phylogenetic positioning of Indian tick vectors and demonstrates the development and applicability of a molecular tool for their identification.

Vector-borne infections are a growing public health concern in Romania, influenced by ecological diversity, climate change, and socioeconomic factors. West Nile virus, tick-borne encephalitis, and Lyme borreliosis represent the most significant threats, with additional risks posed by emerging pathogens, such as leishmaniasis, and the potential reintroduction of malaria. While surveillance systems exist for human cases and, to a lesser extent, vectors, these remain fragmented, underfunded, and limited in their integration across human, veterinary, and environmental health domains. By highlighting both gaps and opportunities, this review provides a forward-looking perspective on strengthening Romania’s capacity to anticipate and manage vector-borne disease threats. Transitioning from reactive surveillance to proactive, prediction-driven strategies will be critical to safeguarding public health in the context of accelerating environmental change.

Introduction: Borrelia bavariensis, a causative agent of Lyme disease, was first reported in South Korea in 2018, yet no complete genome sequence has been described. Here, we present the first whole-genome characterization of B. bavariensis strain KW3, isolated from Ixodes granulatus in the Kangwon region of South Korea. Methods: Genome assembly was achieved using a hybrid approach combining PacBio and Illumina sequencing. Results: The KW3 genome consists of a linear chromosome and 12 plasmids, totaling 1.33 Mbp comprising 1,310 annotated genes. Comparative analyses revealed that strain KW3 is most closely related to Japanese strains NT24 and JAASAAF1029. In multiple phylogenetic trees, strain KW3 consistently clustered within the Japanese clade but formed a distinct subbranch, suggesting regional diversification. Several plasmids showed evidence of fusion or divergence, including lp32-10_lp28-4, lp32-10_lp36, and cp32-6_cp32-12, which displayed partial similarity to plasmids of European Borrelia garinii strains PBes (Germany) and 20047 (France). Key plasmid-borne virulence genes (ospA, ospB, ospC, dbpA, dbpB) were fully conserved in strain KW3 and closely matched those of Japanese strains. In contrast, the vlsE locus, typically located on lp28-8 in B. bavariensis, was absent, possibly due to plasmid loss during in vitro culture. Conclusions: This study provides the first complete genome sequence of B. bavariensis isolate from South Korea and highlights its close relationship to Japanese isolates while revealing unique plasmid features and virulence gene profiles. These findings underscore the importance of continued genomic surveillance to monitor the circulation, evolution, and pathogenic potential of this tick-borne pathogen across East Asia.